Abstract:Objective:To investigate the causal relationship between frailty and kidney function through Mendelian randomiza-tion.Methods:Single nucleotide polymorphisms(SNP)significantly associated with frailty were selected from a large genome-wide as-sociation study(GWAS)database as instrumental variables.Mendelian randomization was performed using three approaches:inverse variance weighted,MR-Egger,and weighted median.The causal link between frailty and kidney function was evaluated using β values and 95%CI.Meanwhile,to ensure the reliability and robustness of the findings,heterogeneity tests,sensitivity analysis,and pleiotropy tests were performed using Cochran's Q test,MR-Egger,MR-PRESSO,and leave-one-out analysis.Results:The IVW estimate revealed a significant negative causal relationship between frailty and blood urea nitrogen(β=-0.030,95%CI:-0.055~-0.006,P=0.013).Similarly,a negative causal relationship was found between frailty and the cystatin C-estimated glomerular filtration rate(β=-0.045,95%CI:-0.065~-0.025,P<0.001).However,no causal relationship was observed between frailty and the urinary albu-min/creatinine ratio,serum creatinine,or chronic kidney disease.Conclusion:This study confirms the causal relationship between frail-ty and kidney function,providing a reference for the prevention and treatment of frailty and kidney function impairment by integration of traditional Chinese and Western medicine.